title: Stimulation of spermatogenesis with recombinant human follicle-stimulating hormone (follitropin alfa; GONAL-f): long-term treatment in azoospermic men with hypogonadotropic hypogonadism.
abstract: OBJECTIVE
  To demonstrate the efficacy and safety of follitropin alfa administered with hCG on spermatogenesis in adult male hypogonadotropic hypogonadism (HH) patients.
  
  
  METHODS
  Phase III, multicenter, open-label, noncomparative.
  
  
  METHODS
  Seven US medical centers.
  
  
  METHODS
  A total of 36 adult males with severe HH.
  
  
  METHODS
  A total of 1,000 U hCG on alternate days for 3 to 6 months, with dose adjustments after 2 months, if necessary, to normalize T levels, followed by follitropin alfa 150 U and hCG on the same alternate days for 18 months, with dose adjustments as necessary.
  
  
  METHODS
  Proportion of patients with sperm density > or =1.5 x 10(6)/mL. Pubertal advancement and long-term safety and tolerability were also evaluated.
  
  
  RESULTS
  In total, 22 of 29 patients (75.9%) who received > or =1 dose of follitropin alfa and 20 of 25 patients (80%) who completed 18 months of hCG + follitropin alfa treatments achieved a sperm concentration > or =1.5 x 10(6)/mL. A sperm concentration >20 x 10(6)/mL was achieved by 8 of 29 men (27.5%). Median sperm concentration at 18 months was 5.2 x 10(6)/mL. Pubertal development continued during the study, and testis volumes increased. Five clinical pregnancies were achieved. Acne (52% of patients) was the most common side effect, and gynecomastia was reported in 10% of patients.
  
  
  CONCLUSIONS
  Long-term treatment of azoospermic HH men using follitropin alfa and hCG is effective for stimulating spermatogenesis and is well-tolerated.
authors.affiliation: Department of Medicine, University of Washington School of Medicine, Seattle, Washington; Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington.
authors.forename: Alvin M
authors.initials: AM
authors.lastname: Matsumoto
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Snyder
authors.affiliation: Department of Medicine, Boston University, Boston, Massachusetts.
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
authors.affiliation: Reproductive Endocrinology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Martin
authors.affiliation: Department of Medicine, Division of Endocrinology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Thomas
authors.initials: T
authors.lastname: Weber
authors.affiliation: Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Stephen
authors.initials: S
authors.lastname: Winters
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Maine Medical Center and Maine Medical Center Research Institute, Portland, Maine.
authors.forename: Daniel
authors.initials: D
authors.lastname: Spratt
authors.affiliation: Clinical Development, EMD Serono, Inc., Rockland, Massachusetts. Electronic address: jim.brentzel@emdserono.com.
authors.forename: Jim
authors.initials: J
authors.lastname: Brentzel
authors.affiliation: Radius Health, Inc., Cambridge, Massachusetts.
authors.forename: Louis
authors.initials: L
authors.lastname: O'Dea
mesh_terms: D000293:Adolescent; D000328:Adult; D053713:Azoospermia / Q000188:drug therapy* / Q000473:pathology; D006063:Chorionic Gonadotropin / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D043373:Follicle Stimulating Hormone, Human / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D015292:Glycoprotein Hormones, alpha Subunit / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000097:blood; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D006063:Chorionic Gonadotropin; D043373:Follicle Stimulating Hormone, Human; D015292:Glycoprotein Hormones, alpha Subunit; D013739:Testosterone